(1) Field of the Invention
The present invention relates to a novel protein having cell growth-stimulating and macrophage chemotactic actions, a preparative method therefor, and use thereof for treating wounds and ulcers.
(2) Related Arts
In the recent years, the average life expectancy tends to be prolonged, and the medical technology for prolonging life has been improved greatly; however, the situation associated with so-called "bedsores" is becoming more serious as the number of permanently bed-ridden people increases.
In addition, wound diseases including such as skin ulcers and dermatitides from the stresses of life or allergies have lately attracted attention. Such diseases have been considered as not fatal with the exception that the affected parts spread over extensively; therefore, an external preparation such as a skin protecting agent, anti-infective agent, or steroid agent is normally applied locally for the treatment. Examples of such a conventional wound-treating external preparation include a zinc oxide ointment, "Solcoseryl" (Trademark) ointment (an extract from hemolysed blood of young cattle), "Zildasac" (Trademark) ointment (bendazac), "Elase" (Trademark) ointment (fibrinolysin, DNase), "Cartabes" (Trademark) (carbazochrome alkyldiaminoethylglycine hydrochloride), AD ointment (an enforced cod-liver oil), "Alkixa" (Trademark) ointment (aluminum chlorohydroxy allantoinate) and "Oronine" (Trademark) ointment (an analog of chlorohexidine), and the like. However, these treatments are not basic but only symptomatic.
A close look at the tissue disability caused by a would and its repairing process will reveal that the most important elements required for the treatment are the contraction, the epithelization and the formation of granulation tissue; therefore, recent wound-treating drugs are trending towards cell growth-stimulating and tissue repair-accelerating preparations which may be applied clinically.
Typical examples of such a preparation include "Reflap" (Trademark) ointment (lysozyme chlorides), "Olcenon" (Trademark) ointment (tretinoin-tocoferil), "Actosin" (Trademark) ointment (bucladesine sodium), or the like; however, presently available preparations are less than satisfactory and there is a continuing and growing demand for improved types of wound-treating drugs.
In view of the foregoing situation the present inventors have intensively investigated the treatment of wound diseases of skin from various points of view, and as a result, found that hydantoin compounds having aldose reductase-inhibitory action are effective for preventing and treating skin ulcers caused by diabetes complications [Jap. Pat. No. Hei 3 (A.D. 1991)-215435(A)], and kininogenase from human urine are effective for preventing and treating a skin ulcer based on blood flow disorder [Jap. Pat. No. Hei 5 (A.D. 1993)-163158(A)]. In addition, the inventors have found that a protein obtained from the cultured cell body of various strains including genus of Clostridium has cell growth-stimulating action, and an ointment containing the protein exhibits remarkable wound-healing effect on the full-thickness skin wounds model in rats [Jap. Pat. No. Hei 5 (A.D. 1993)-38000(B)].